Hemopoietic insufficiency secondary to cancer therapy represents a major obstacle to the administration of potentially curative therapeutic regimens. The microsinusoidal circulation of the marrow plays a vital role in supporting the lodgement, proliferation and differentiation of hemopoietic stem cells. Tumoricidal doses of radiation may damage endothelial cells which are probably of key importance to the proliferation and selective release of mature functional blood cells from the marrow. Thus, we propose to study the repopulation of endogenous stem cells, erythropoietic tissue, and endothelial cells in the irradiated mouse and rat femur. At various times for a year after incremental doses of radiation are administered, irradiated femoral marrow cells will be obtained for assay of CFUs (Colony forming units-spleen) or for the proliferation of endothelial cells in culture. Erythropoiesis and blood flow in the irradiated femur will also be determined. Once we establish the dose of radiation that prevents repopulation of hemopoietic tissue, we will ascertain if that same dose inhibits the proliferative capacity of endothelial cells and/or interdicts the flow of blood to the marrow. With the effect of radiation as an index, we then propose to compare the effects of cycle-independent chemotherapeutic agents. Elucidation of the mechanisms of damage to the hemopoietic microenvironment may permit the design of therapy that will prevent bone marrow failure in patients with neoplastic diseases.